What does detection of the RHD (Rh Blood Type D) gene indicate?

Detection of the RHD Gene

Detection of the RHD gene indicates the presence of genetic material coding for the RhD antigen, most commonly used to determine fetal RhD blood type status in pregnant women or to confirm an individual's RhD-positive blood type at the genetic level.

Primary Clinical Application: Fetal RhD Genotyping in Pregnancy

The most common reason for RHD gene testing is noninvasive prenatal determination of fetal RhD status in RhD-negative pregnant women to guide targeted anti-D prophylaxis administration 1, 2.

How the Test Works

• Cell-free fetal DNA circulates in maternal plasma starting early in pregnancy, released from apoptotic placental trophoblastic cells 2, 3
• DNA extracted from maternal plasma is analyzed using real-time PCR to detect RHD-specific sequences (typically exons 7 and 10) 3, 4
• The test has excellent accuracy: 97.2% sensitivity and 96.8% specificity overall, with accuracy of 99.1% in first and second trimesters and 98.1% in third trimester 1

Clinical Significance for Pregnancy Management

If the RHD gene is detected in maternal plasma of an RhD-negative woman, this indicates the fetus is RhD-positive and the mother requires anti-D prophylaxis 1, 5.

Key management points:

• RhD-negative mothers carrying RhD-positive fetuses are at risk for alloimmunization, which can cause hemolytic disease of the fetus and newborn 2, 3
• Anti-D immunoglobulin (RhIG) should be administered within 72 hours after delivery of an RhD-positive infant 5
• Antenatal anti-D prophylaxis is recommended during pregnancy for at-risk women 3, 4
• If RHD gene is NOT detected, the fetus is RhD-negative and the mother does NOT require anti-D prophylaxis, avoiding unnecessary administration of blood products 2, 3

Timing and Reliability

• Testing can be performed reliably beginning in the second trimester (around 25 weeks gestation) with near-perfect accuracy 6, 4
• First trimester testing has slightly lower sensitivity with occasional false negatives 6
• In one large validation study of 373 samples, there was only 1 false positive and 0 false negatives 3

Important Caveats and Pitfalls

Genetic Complexity of RHD

A critical pitfall is that not all RhD-negative phenotypes result from complete RHD gene deletion 2.

• Some RhD-negative individuals possess RHD gene fragments or pseudogenes (particularly common in African populations) 2
• This can cause false-positive results if the test only detects RHD presence without distinguishing functional from non-functional variants 2
• Modern comprehensive tests differentiate these alleles to provide accurate results in multi-ethnic populations 2

Maternal RHD Gene Interference

• Approximately 3% of samples may be indeterminate due to maternal RHD gene fragments in RhD-negative women 3
• In the validation study, 12 of 373 samples could not be determined, all due to maternal RHD gene presence 3

Other Clinical Applications

Blood Transfusion Context

While less common, RHD genotyping can confirm RhD-positive blood type at the genetic level:

• Useful when serologic testing is ambiguous 1
• Helps identify individuals with variant RHD alleles who may require special transfusion considerations 1
• Patients with partial C antigen variants (like RHDDIIIa-CE or RHCECeRN alleles) should receive C-negative red cells to prevent alloimmunization 1

Emergency Transfusion Scenarios

• In massive hemorrhage, group O RhD-negative blood is preferred for emergency transfusion when patient blood type is unknown 1
• RHD genotyping is not used in acute settings but may guide subsequent transfusion management 1